Tendon and Ligament-Related Genes Associate with Elite Status in Rugby

INTRODUCTION: Elite rugby has one of the highest reported injury incidences of any professional sport (Brooks and Kemp, 2008). Some of the most severe injuries are those affecting tendon and ligament (Brazier et al., 2019), and therefore potentially the most debilitating to a player and playing squad. Achilles tendon pathology and anterior cruciate ligament rupture are multifactorial conditions. The aetiology of these injuries are due to a number of intrinsic and extrinsic factors, with a growing body of evidence suggesting that some inter-individual variability in injury susceptibility may be due to genetic variation (September et al., 2006). Elite rugby athletes (RA) potentially have a unique ability to recover from or withstand performance limiting or career-ending soft tissue injury to achieve their elite status. Thus, it was hypothesised that RA would possess genotypes associated with reduced soft tissue injury compared to a non-athlete control population. METHODS: Participants from the RugbyGene project were elite Caucasian male RA (n = 636; mean (standard deviation) height 1.85 (0.07) m, mass 101 (12) kg, age 28 (7) yr), including 535 rugby union athletes and 104 rugby league athletes. Non-athletes (NA) were 722 Caucasian men and women (58% female; height 1.69 (0.10) m, mass 72 (14) kg, age 41 (23) yr). PCR of genomic DNA was used to determine genotypes using TaqMan probes, then groups were compared using Χ2 and odds ratio (OR) statistics, with alpha set at P<0.05. RESULTS: COLGALT1 rs8090 AA genotype was more frequent in RA (27%) compared to NA (23%) (Χ2 = 12.6, P = 0.002; OR = 1.48, 95% confidence intervals (CI) = 1.1-2.0), and NID1 rs4660148 TT genotype was more frequent in RA (10%) compared to NA (6%; Χ2 = 14.5, P = 0.001; OR = 1.6, 95% CI = 1.1-2.4). For MIR608 rs4919510, CC genotype was more frequent in RA (63%) compared to NA (56%; Χ2 = 16.4, P = 0.0003; OR = 1.7, 95% CI = 1.1-2.6). For COL3A1 rs1800255, the A-allele was more frequent in RA (26%) compared to NA (23%) due to a greater frequency of GA genotype (39%) compared to NA (33%; Χ2 = 9.0, P = 0.011; OR = 1.3, 95% CI = 1.0-1.6). There were no genotype differences between RA and NA for the COL1A1 rs1800012 variant. CONCLUSION: We provide evidence for elite RA possessing a possible protective genetic profile regarding tendon and ligament injury risk. Notably, more frequent COLGALT1 AA, NID1 TT, MIR608 CC and COL3A1 GA genotypes in RA suggest a lower genetic risk of injury could enhance career success in rugby. Future research should focus on establishing how gene variants affect the collagen and extracellular matrix structures, as this may underline appropriate interventions for a more individualised injury prevention and management plan.